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Updated: Nov 8, 2025
Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
Targeting Runt-Related Transcription Factor 1 Prevents Pulmonary Fibrosis and Reduces Expression of Severe Acute
Michael O'Hare1, Dhanesh Amarnani1, Hannah A B Whitmore1
1Schepens Eye Research Institute of Mass Eye and Ear, Boston, Massachusetts, and the Department of Ophthalmology at Harvard Medical School, Boston, Massachusetts.
Abstract:
Pulmonary fibrosis (PF) can arise from unknown causes, as in idiopathic PF, or as a consequence of infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current treatments for PF slow, but do not stop, disease progression. We report that treatment with a runt-related transcription factor 1 (RUNX1) inhibitor (Ro24-7429), previously found to be safe, although ineffective, as a Tat inhibitor in patients with HIV, robustly ameliorates lung fibrosis and inflammation in the bleomycin-induced PF mouse model. RUNX1 inhibition blunted fundamental mechanisms downstream pathologic mediators of fibrosis and inflammation, including transforming growth factor-β1 and tumor necrosis factor-α, in cultured lung epithelial cells, fibroblasts, and vascular endothelial cells, indicating pleiotropic effects. RUNX1 inhibition also reduced the expression of angiotensin-converting enzyme 2 and FES Upstream Region (FURIN), host proteins critical for SARS-CoV-2 infection, in mice and in vitro. A subset of human lungs with SARS-CoV-2 infection overexpress RUNX1. These data suggest that RUNX1 inhibition via repurposing of Ro24-7429 may be beneficial for PF and to battle SARS-CoV-2, by reducing expression of viral mediators and by preventing respiratory complications.
Insights
A novel runt-related transcription factor 1 (RUNX1) inhibitor effectively reduces lung fibrosis and inflammation in mice. This RUNX1 inhibitor also lowers key proteins for SARS-CoV-2 infection, suggesting dual therapeutic potential.
Area of Science:
- Pulmonary Medicine
- Virology
- Molecular Biology
Background:
- Pulmonary fibrosis (PF) is a progressive lung disease with limited treatment options.
- Infections, including SARS-CoV-2, can trigger or exacerbate PF.
- Current PF treatments only slow disease progression.
Purpose of the Study:
- To investigate the therapeutic potential of a RUNX1 inhibitor (Ro24-7429) for pulmonary fibrosis.
- To explore the effect of RUNX1 inhibition on SARS-CoV-2 infection pathways.
Main Methods:
- Utilized the bleomycin-induced PF mouse model.
- Administered a RUNX1 inhibitor (Ro24-7429) to evaluate its effects on lung fibrosis and inflammation.
- Assessed the impact of RUNX1 inhibition on fibrotic mediators (TGF-β1, TNF-α) in vitro.
- Examined the effect of RUNX1 inhibition on SARS-CoV-2 host proteins (ACE2, FURIN) in vivo and in vitro.
Main Results:
- RUNX1 inhibition robustly ameliorated lung fibrosis and inflammation in the mouse model.
- RUNX1 inhibition reduced key fibrotic and inflammatory mediators (TGF-β1, TNF-α) in cultured lung cells.
- RUNX1 inhibition decreased the expression of ACE2 and FURIN, critical for SARS-CoV-2 entry.
- Overexpression of RUNX1 was observed in a subset of human lungs with SARS-CoV-2 infection.
Conclusions:
- Repurposing the RUNX1 inhibitor Ro24-7429 shows promise for treating pulmonary fibrosis.
- RUNX1 inhibition may offer a dual benefit by combating PF and reducing SARS-CoV-2 infectivity.
- Targeting RUNX1 could be a novel strategy for managing respiratory viral infections and their complications.
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